The detection of biological and chemical species is central to many areas of healthcare and the life sciences, ranging from uncovering and diagnosing disease to the discovery and screening of new drugs. The development of advanced devices that enable reliable and sensitive detection of these species is therefore important.
Central to detection is the signal transduction associated with selective recognition of a biological or chemical species of interest. Planar semiconductors can serve as the basis for chemical and biological sensors in which detection can be monitored electrically and/or optically. For example, a planar field effect transistor (FET) can be configured as a sensor by modifying the gate oxide (without gate electrode) with molecular receptors or a selective membrane for the analyte of interest. Binding of a charged species then results in depletion or accumulation of carriers within the transistor structure. An attractive feature of such chemically sensitive FETs is that binding can be monitored by a direct change in conductance or related electrical property, although the specificity for different biological molecules is limited.
The physical properties limiting sensor devices fabricated on planar semiconductors can be readily overcome by exploiting nanoscale FETs. In this regard, nanoscale sensors based on nanowires and nanotubes have received considerable recent attention. Nanowires and nanotubes have the potential for very high sensitivity (single-molecule detection in some cases) since the depletion or accumulation of charge carriers, which are caused by the binding of a charged molecule at the surface of the nanowire/nanotube, can affect the entire cross-sectional conductional pathway of these nanostructures. Furthermore, the small size of the nanowires and nanotubes combined with recent advances in assembly suggest that dense arrays of sensors could be prepared.
Research in this area has shown that nanowire FET devices can be functionalised with immobilised probe molecules such as surface receptors for the detection of specific molecular species in solution. The first published example demonstrating the ability of a nanowire FET to detect species in solution dates back to 2001, where a p-type Si nanowire device was used as a pH sensor by chemical modification of the silicon oxide surface [Y. Cui et al, Science, 293, 1289 (2001)]. This silicon nanotube-based device was subsequently modified to enable it to detect the presence of various proteins.
Using the same principle, such sensors have been used as tools for drug discovery, where the binding or inhibition of binding was solved as an increase or decrease in conductance, respectively [W. U. Wang et al, PNAS, 102, no. 9, 3208 (2005)]. In addition, single-stranded DNA fragments have been detected as an increase in conductance using a nanowire surface modified with peptide nucleic acid (PNA) receptors [J. Hahm et al, Nano Letters, 4, no. 1, 51 (2004)].
Further research has demonstrated the detection of a virus using an antibody receptor [F. Patolsky et al, PNAS, 101, no. 39, 14017 (2004)], wherein the binding and the release of the virus particles caused a change in the conductance of the nanowire device.
Whilst nanowire-based sensors offer a number of key benefits with respect to other technologies (direct, label-free, real-time detection, ultrahigh sensitivity, high selectivity, potential for integration into arrays on a massive scale), the above-mentioned devices also have their drawbacks. Reports of the use of FETs to directly sense the presence of biological molecules have shown inconsistent results, partly due to the complexity of the charged species being measured. In addition, such devices cannot be reused after the sensing event and must therefore be disposed of. Furthermore, the correct attachment of the receptor molecules to ensure highly specific binding requires sometimes complicated surface functionalisation.
Development of surface chemistry to couple biological molecules to a surface is a common problem in the development of sensors, and numerous solutions exist. One solution exploits the capacity of certain types of lipid molecules to form membranes, for example the plasma membrane that encloses the cytoplasm of many types of biological cells. Some types of receptor molecules have evolved to bind their analyte when they are embedded in lipid membranes. This specific receptor-analyte recognition leads to an alteration of some electrochemical property of the membrane, such as transmembrane conductance or capacitance.
Recent work has suggested that lipid membranes can serve as functional interfaces between the biological analyte and the nanoelectronic sensor [N. Misra et al, PNAS, 106, no. 33, 13780 (2009)]. In this study, Si nanowires were covered by a continuous lipid bilayer membrane to form a shield between the nanowire and the species in solution. The incorporation of transmembrane peptide pores enabled ionic species to transport across the membrane and generate an ionic-electronic signal. This work suggests that lipid membrane-coated nanowire devices incorporating functional membrane proteins could serve as versatile platforms for developing biosensors that are based on the functionality of the transmembrane protein pores.
The listing or discussion of a prior-published document or any background in this specification should not necessarily be taken as an acknowledgement that the document or background is part of the state of the art or is common general knowledge. One or more aspects/embodiments of the present disclosure may or may not address one or more of the background issues.